This project is a study of mechanisms involved in the pulmonary toxicity of paraquat, an herbicide used in agriculture throughout the world. The potentiation by 1-isoproterenol of paraquat lethality (Ann. Rep. for 1975-76) can be explained by a decreased glomerular filtration rate and a reduced renal plasma flow: 1-isoproterenol reduced the "average body clearance" of inulin and both acidic (p-aminohippuric acid) and basic (paraquat and N-methylnicotinamide) compounds. Nonreversible binding of 3H-DL-epinephrine (5 x 10 to the minus 4th power M) to rat lung microsomes in vitro was increased about 30% by paraquat (5 x 10 to the minus 3rd power M), was partially blocked by either superoxide dismutase (100 microgram/ml, 63%) or catalase (30 microgram/ml, 20-30%), and more completely blocked (70-86%) by the combination of superoxide dismutase and catalase. Nonreversible binding of epinephrine to lung microsomes was inhibited almost completely by glutathione (10 to the minus 3rd power M, 96%) or ascorbic acid (10 to the minus 3rd power, M, 89%). However, extrapolation of these in vitro findings to paraquat toxicity in vivo is not justified since nonreversible binding of 3H-DL-epinephrine did not occur in incubations with lung slices or homogenates. BIBLIOGRAPHIC REFERENCE: Maling, H.M., Saul, W., Williams, M.A., Brown, E.A.B. and Gillette, J.R.: On the mechanism of the potentiation by beta adrenergic agonists of paraquat toxicity in rats and mice. In Autor, Ann (ed.): Biochemical Mechanisms of Paraquat Toxicity. New York, Academic Press, 1977, in press.